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Biomedical subjects

B Wonke

Publications and source records attributed to B Wonke.

At least 73 records · Page 4Linked to original sources
PubMed1990

Antibody to hepatitis C virus in multiply transfused patients with thalassaemia major.

Seventeen of 73 (23.3%) multiply transfused patients with thalassaemia major (age range, 1-39 years) tested positive for antibody to hepatitis C virus (anti-HCV). Eleven of the 24 patients regularly transfused in countries outside Britain were anti-HCV seropositive; only six of the 49 regularly transfused in Britain were seropositive. The incidence of anti-HBs and anti-HBc was similar to that of anti-HCV in both the British and foreign patients. The anti-HCV seropositive patients showed significantly higher plasma aspartate aminotransferase activities (AST), mean (SD) 10.2 (70.3) U/l, and serum ferritin concentrations, 4067 (2708) micrograms/l, than the anti-HCV seronegative patients (AST, 33.9 (15.6) U/l; serum ferritin 2051 (2092) U/l), respectively. Among the 36 patients who had earlier undergone liver biopsy 10 of 21 with histological features of chronic active hepatitis or cirrhosis, or both, were seropositive for anti-HCV whereas only one of 15 without histological evidence of chronic viral hepatitis was seropositive for anti-HCV. It is concluded that HCV is a major cause of chronic hepatitis in patients with thalassaemia major and is associated with raised AST activity and serum ferritin concentration compared with patients seronegative for anti-HCV.

Adolescent↗
PubMed1990

High incidence of cardiomyopathy in beta-thalassaemia patients receiving regular transfusion and iron chelation: reversal by intensified chelation.

Cardiac scintigraphy has been performed in 60 beta-thalassaemia major patients aged 8-35 years who received regular blood transfusions and subcutaneous desferrioxamine (DFX) chelation. Fifty-seven showed no clinical, radiological or electrocardiographic evidence of heart disease and 3 had clinically apparent cardiac failure. Twenty-two patients (37%) showed severe cardiac functional impairment defined by a resting left ventricular ejection fraction (LVEF) less than 45% and/or a drop of greater than 12% on stress, while 19 were normal and 19 had a mild abnormality. There was no significant correlation between abnormality of LVEF and age, serum ferritin, number of units transfused, dose and duration of subcutaneous DFX therapy, liver disease or sexual maturation. Non-compliant patients (defined as the use of subcutaneous DFX less than 4 times weekly) generally showed worse cardiac function. Repeat study on 17 patients after 6-28 months of better compliance with subcutaneous or intravenous DFX (using an indwelling catheter) showed a significant overall improvement in LVEF associated with a significant drop in serum ferritin. We conclude that cardiac scintigraphy uncovers a high incidence of cardiac functional abnormality in asymptomatic, well-transfused thalassaemia patients, particularly those poorly compliant with chelation. Those with poor LVEF results should be offered intensive chelation therapy to improve cardiac function.

Adolescent↗
PubMed1989

Results of long-term subcutaneous desferrioxamine therapy.

Regular subcutaneous desferrioxamine therapy has prolonged the life and reduced the incidence of cardiac, endocrine and liver complications of iron overload in patients with thalassaemia major and other refractory transfusion-dependent anaemias. Its full impact will be apparent only when patients who began this treatment as children 10 years ago reach adult life. The major problems with s.c. DF therapy are its cost and the difficulty of patient compliance with a painful and cumbersome method of administration. Attempts to maintain normal iron stores in these patients has resulted in significant toxicity caused by the excessive use of DF. Although recent studies have shown that long-term subcutaneous calcium diethylene triamine penta-acetic acid (Ca-DTPA) can be used as an effective alternative to s.c. DF (Wonke et al, 1988), this treatment presents additional potential problems of zinc depletion which can be prevented only by careful management. The prospects of an inexpensive, orally active iron chelator are now real (Kontoghiorghes and Hoffbrand, 1988) and it is to be hoped that long-term results at least as good as those with s.c. DF will be achievable. Such oral chelators may be available to a far wider group of patients, than s.c. DF, and the problems of cost and compliance may be diminished.

Deferoxamine↗
PubMed1989

Reversal of desferrioxamine induced auditory neurotoxicity during treatment with Ca-DTPA.

Auditory neurotoxicity occurred in 13 (26%) of 50 evaluable patients receiving long term desferrioxamine chelation. In five of these patients, all of whom were receiving high doses of desferrioxamine, the toxicity caused deafness. These five patients were treated with subcutaneous calcium diethylene triamine pentacetic acid (Ca-DTPA) with zinc supplements instead of desferrioxamine, and their hearing improved during periods of seven to 19 months. Their serum ion concentrations remained unchanged. We suggest that all patients receiving long term desferrioxamine should have audiometric assessments at 6-12 monthly intervals. Ca-DTPA with oral zinc supplements should be considered as alternative to desferrioxamine as an iron chelating treatment in patients with auditory neurotoxicity.

Adolescent↗
PubMed1989

Intradermal hepatitis B vaccine in thalassaemia and sickle cell disease.

Thirty two patients with beta thalassaemia and sickle cell disease who were having regular blood transfusions were selected to test the efficacy and immunogenicity of low dose (2 micrograms or 0.1 ml) intradermal hepatitis B vaccine compared with the standard (20 micrograms or 1 ml) intramuscular dose. There was no significant difference in the rates of seroconversion, seroconversion had occurred in all patients by seven months. There were no significant differences in antibody titres between the intramuscular and intradermal groups at 1, 2, and 6 months. Although the titres were significantly higher in the intramuscular group at seven months and at 12-18 months, the antibody titre in the intradermal group did not fall below 10 IU/l. The results of this study suggest that low dose intradermal hepatitis B vaccination is an effective and economical way of stimulating an immune response in patients with beta thalassaemia and sickle cell disease.

Anemia, Sickle Cell↗
PubMed1988

Induction of spermatogenesis in thalassaemia.

In an attempt to induce or to augment pubertal development and to achieve spermatogenesis, 10 gonadotropin-deficient thalassemic patients 15 to 23 years of age (mean 18.9 years) were treated with exogenous gonadotropins for 1 to 4 years (mean 2.1 years). Seven patients produced sperm during human chorionic gonadotropin (hCG) treatment given for 6 to 14 months. However, full spermatogenesis was achieved only when human menopausal gonadotropin was added to hCG regimen. In one patient, despite cessation of gonadotropin treatment, sexual potency, libido, and spermatogenetic capacity were maintained during the past 2 1/2 years. Our study indicates that it is possible to induce or to restore spermatogenesis in the majority of thalassemic patients and that gonadotrope cells may not be irreversibly damaged by iron deposition.

Adolescent↗
PubMed1988

Gonadal function in patients with beta thalassaemia major.

Endocrine studies were made on 23 female patients aged 13 to 29 years, with delayed puberty or primary amenorrhoea and beta thalassaemia major, and 12 healthy controls, of whom six were prepubertal and six were in Tanner's stage 3-4. Each patient and control received a single intravenous dose of 100 micrograms gonadotrophin releasing hormone (GnRH), and one week later, 10 U/kg body weight of human menopausal gonadotrophin (hMG) to stimulate ovarian function. The patients had decreased gonadotrophin reserves when compared with those of normal controls, only one of 23 patients had an intact luteinising hormone and follicle stimulating hormone response. Most of the thalassaemic patients with delayed puberty showed normal gonad response to human menopausal gonadotrophin (hMG), but three had very low responses, when compared with that of controls. The gonadal failure was even more severe in four of six patients with primary amenorrhoea. It is important to assess hypothalamic-pituitary-gonadal function in young women with beta thalassaemia major, so that those with glandular dysfunction may be started on replacement therapy.

Adolescent↗
PubMed1988

Prediction of consanguinity using human DNA fingerprints.

DNA fingerprinting was performed to verify the pedigree structure of a family under investigation for an unusual case of beta thalassaemia. A higher than expected proportion of hypervariable bands was shared by the proband and his mother, leading to suspicion that the child had been the product of a consanguineous mating. Further analysis of the mother's brother showed that he was almost certainly the proband's father.

Child, Preschool↗
PubMed1988

Hypothalamic-pituitary-gonadal axis in thalassemic patients with secondary amenorrhea.

Eight thalassemic patients, aged 24-35 years, who developed amenorrhea 2-15 years after menarche, were studied. Mean basal serum LH and FSH levels and the peak levels after gonadotropin-releasing hormone were significantly less than corresponding values in normal controls. All patients showed low basal serum levels of estradiol and six had a poor or absent response to human menopausal gonadotropin. One subject had intact pituitary-gonadal function and one patient had an impaired LH and FSH response to gonadotropin-releasing hormone in the presence of a significant increase of estradiol after human menopausal gonadotropin stimulation. The findings regarding pituitary hormones other than gonadotropins suggest that iron overload damages tropic cells unequally and inconsistently. We conclude that both pituitary and gonadal damage may be responsible for the secondary amenorrhea in thalassemic patients.

Adult↗
PubMed1987

Effective chelation of iron in beta thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one.

The main iron chelator used for transfusional iron overload is desferrioxamine, which is expensive, has toxic side effects, and has to be given subcutaneously. An orally active iron chelator is therefore required. The effects of oral 1,2-dimethyl-3-hydroxypyrid-4-one on urinary iron excretion were studied in eight patients who had received multiple transfusions: four had myelodysplasia and four beta thalassaemia major. Different daily doses of the drug up to 100 mg/kg/day, alone or in combination with ascorbic acid, were used. In three patients with thalassaemia the effect of the drug was compared with that of subcutaneous desferrioxamine at the same daily dose. In all eight patients a single dose of oral 1,2-dimethyl-3-hydroxypyrid-4-one resulted in substantial urinary iron excretion, mainly in the first 12 hours. Urinary iron excretion increased with the dose and with the degree of iron loading of the patient. Giving two or three divided doses over 24 hours resulted in higher urinary iron excretion than a single dose of the same amount over the same time. In most patients coadministration of oral ascorbic acid further increased urinary iron excretion. 1,2-Dimethyl-3-hydroxypyrid-4-one caused similar iron excretion to that achieved with subcutaneous desferrioxamine at a comparable dose. In some cases the iron excretion was sufficiently high (maximum 99 mg/day) to suggest that a negative iron balance could be easily achieved with these protocols in patients receiving regular transfusions. No evidence of toxicity was observed on thorough clinical examination or haematological and biochemical testing in any of the patients. None of the patients had any symptoms that could be ascribed to the drug. These results suggest that the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one is as effective as subcutaneous desferrioxamine in increasing urinary iron excretion in patients loaded with iron. Its cheap synthesis, oral activity, and lack of obvious toxicity at effective doses suggest that it should be developed quickly and thoroughly tested for the management of transfusional iron overload.

Administration, Oral↗
PubMed1987

Iron state and hepatic disease in patients with thalassaemia major, treated with long term subcutaneous desferrioxamine.

Liver biopsies were performed on 51 regularly transfused patients with beta thalassaemia, age range 5-36 (mean 18.6) years, who had received regular subcutaneous desferrioxamine (DFX) treatment for periods between one and eight years (40 for eight years). The biopsy specimens were examined by light microscopy and immunofluorescence for hepatitis B virus surface and core antigens (HBsAg and HBcAg), and the iron content was determined chemically. The results were compared with serum ferritin concentration and aspartate transaminase (AST) activity and with hepatitis B virus serology. Biopsy specimens, in which chemical liver iron had been determined in 12, were also available from 17 patients. Mean serum ferritin (+/- SD) had fallen from 5885 (3245) micrograms/l to 1638 (976) micrograms/l in 36 patients after eight years' chelation, while mean (+/- SD) liver iron concentration had fallen from 2945 (900) micrograms/100 mg dry weight to 857 (435) micrograms/100 mg dry weight in 12 of them. All biopsy specimens examined were negative for HBs and HBc antigens. The presence of histological features of hepatitis was associated with increased liver iron content, increased fibrosis, and with progression of fibrosis between the two biopsies. Procollagen III peptide was assayed in 28 patients but did not correlate with the degree of hepatitis, fibrosis, or with chemical liver iron content. We conclude that with regular subcutaneous DFX, mean concentrations of serum ferritin and liver iron are maintained in these patients at about five and 10 times the normal value, respectively, and that progression of liver damage is more likely to be due to viral hepatitis, presumably related to the parenterally transmitted non-A, non-B agents than to iron overload.

Adolescent↗
PubMed1986

The development of diabetes mellitus and chronic liver disease in long term chelated beta thalassaemic patients.

We studied 29 patients with thalassaemia major who had received intensive chelation for between 6.2 and 8.8 years. All patients had normal oral glucose tolerance tests before subcutaneous chelation therapy was introduced and 22 of 29 patients had normal liver function tests. At the end of the period of study 12 patients still had normal oral glucose tolerance (7 with normal liver function tests and 5 with chronic active hepatitis). On the other hand, 11 patients had developed impaired glucose tolerance tests (3 patients had normal liver function tests, 5 with chronic active hepatitis and 3 with cirrhosis), and 6 patients had developed frank diabetes mellitus (one with chronic active hepatitis and 5 with cirrhosis). Patients with chronic active hepatitis showed 91% positivity for one or more hepatitis B markers whilst all patients with cirrhosis were positive. Ferritin levels before subcutaneous chelation in patients with normal oral glucose tolerance tests were lower than in those patients with abnormal oral glucose tolerance or diabetes (P less than 0.05) but none had normal serum ferritin levels. In addition, a positive correlation was found between glucose area under the curve after chelation therapy and serum ferritin levels (r = 0.47, P less than 0.01). It is apparent that long term chelation therapy does not prevent the development of abnormal oral glucose tolerance in chronically transfused patients. More intensive chelation therapy is needed to prevent tissue damage. Chronic liver disease may have an important role to play in the deterioration of glucose tolerance.

Adolescent↗